Objectives

To identify novel plasma biomarkers of progressive fibrosing interstitial lung disease and develop a proteomic signature to predict this phenotype.

Background

Progressive fibrosing interstitial lung disease (ILD) is a devastating condition characterized by parenchymal scar formation, leading to deteriorating lung function and early death. Whereas almost all patients with idiopathic pulmonary fibrosis (IPF) progress, a variable proportion of patients with other common ILDs, including connective tissue disease associated ILD, chronic hypersensitivity pneumonitis, and unclassifiable ILD, develop progressive fibrosing ILD. There are criteria that effectively identify those experiencing ILD progression. However, the criteria do not allow patients who are at risk to be identified before progression occurs.

Several blood-based biomarkers have been linked to differential progression in patients with IPF and other fibrosing ILDs. Inflammatory signaling also appears to have a prominent role in fibrotic-predominant ILDs. As such, cytokines, interleukins, and other immune mediators might serve as useful biomarkers of progressive fibrosing ILD. The PF-ILD Proteomics study was a targeted investigation of inflammation-related proteins to identify and validate novel biomarkers of progressive fibrosing ILD in patients with fibrotic connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, and unclassifiable ILD.

Participants

Eligible patients had fibrotic ILD due to connective tissue disease associated ILD, chronic hypersensitivity pneumonitis, or unclassifiable ILD, and provided a research blood draw at the University of California Davis (UC Davis), University of California San Francisco (UCSF), or University of Texas Southwestern Medical Center (UTSW).

The discovery cohort comprised 385 patients and the validation cohort comprised 204 patients.

Design

PF-ILD Proteomics was a multicenter cohort analysis study. Peripheral blood was collected from consenting patients and plasma was isolated according to center-specific protocols. Relative plasma concentrations for 368 biomarkers were determined with use of a semi-quantitative, targeted proteomic platform. Patients from UC Davis and UCSF comprised the discovery cohort and those from UTSW comprised the validation cohort.

Patients who were alive with less than 10% relative decline in forced vital capacity (FVC) at 12 months-after blood draw were considered to have non-progressive ILD. Patients who died of any cause, underwent lung transplant, or experienced 10% or greater relative FVC decline within 12 months of blood draw were deemed to have progressive fibrosing ILD.

Conclusions

17 plasma biomarkers of progressive fibrosing interstitial lung disease were identified and showed consistent associations across ILD subtypes.

Bowman WS, Newton CA, Linderholm AL, et al. Proteomic biomarkers of progressive fibrosing interstitial lung disease: a multicentre cohort analysis. Lancet Respir Med. 2022; 10(6):593-602. doi:10.1016/S2213-2600(21)00503-8

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